Molecular Basis for the Morphogenesis of the Inner Ear

Deafness &Other Communication Disorders

Investigators

Linked publications & trials

Abstract

The goal of this project is to understand the molecular basis for the normal development of the vertebrate inner ear. Our major accomplishment this year was identifying the role of Bone Morphogenetic Proteins (BMP) in the development of the inner ear using a BMP antagonist, Noggin. Exogenous Noggin was delivered to the developing chicken inner ear by microinjection of avian retrovirus encoding the Noggin cDNA or by implanting beads coated with Noggin protein. The treated inner ears were analyzed for gross developmental changes using a paint-filling technique, as well as for gene expression using whole mount and section in situ hybridization. Our results show that exogenous Noggin perturbed the normal development of the semicircular canals as well as gross patterning of sensory organs. These results also suggest that there is a continual requirement for BMPs during different phases of semicircular canal development. In addition, in collaboration with Eric Green in NHGRI and other investigators at NIDCD, we have characterized the phenotype of Pendrin knock out mice. Pendrin was recently identified to be the gene responsible for the most common form of syndromic deafness, Pendred syndrome, as well as a non-syndromic form of deafness. Heterologous expression studies show that PENDRIN functions as a chloride or iodide transporter. Pendrin knock out mice are deaf with variable vestibular defects. The cause of deafness is caused by initial swelling of the membranous labyrinth resulting from fluid imbalance of the endolymph that eventually leads to sensory hair cell degeneration. Other ongoing projects in the laboratory include investigating the phenotypes of mutant and knock out mice with inner ear defects.